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Saturday, November 10, 2018

Samantha Zyontz on CRISPR Adoption

Posted by
Lisa Ouellette

Pierre Azoulay's recent Twitter thread on students from the MIT Sloan TIES PhD program who are currently on the market alerted me to Sam Zyontz's interesting work on the CRISPR genome editing tool. CRISPR has captivated the patent world due to the fight between the University of California and MIT's Broad Institute over key patent rights—Jake Sherkow summarized the dispute in May and reflected on the Federal Circuit's decision in September. But CRISPR is of course also interesting to innovation scholars due to the revolutionary nature of the technology itself (this is why the patent rights were worth fighting for), which has the potential to applied to a tremendous variety of applications. Using data on researchers who attempt to experiment with CRISPR and the smaller number who succeed in publishing new findings using the technology, Zyontz has produced some fascinating findings on hurdles to technological diffusion.

Zyontz's work was made possible because of the nonprofit global plasmid repository Addgene, which received the basic biological tools for CRISPR from researchers at the University of California and the Broad Institute in 2012 and 2013. Since then, researchers have had easy access to CRISPR tools for the low cost of $65 per plasmid.

For her 2016 Master's thesis, Technological Breakthroughs, Entry, and the Direction of Scientific Progress: Evidence from CRISPR/Cas9, Zyontz did not yet have information about the identities of the ordering labs, but she combined data about what kinds of plasmids were being ordered from Addgene (through 2014) with CRISPR-related publications in Elsevier's Scopus database (through 2015). Her main finding is that the increase in mammalian genetic engineering research was primarily due to new researchers attracted to the genetic engineering field rather than to increased productivity of researchers who had been working on mammalian models or a shift by researchers who had previously published on bacterial genetic engineering.

In a subsequent paper with Neil Thompson, Who Tries (and Who Succeeds) in Staying at the Forefront of Science: Evidence from the DNA-Editing Technology, CRISPR (posted in 2017), Zyontz was able to match individual labs that requested CRISPR plasmids with their subsequent publications, allowing a more direct examination of which researchers succeeded in adopting the technology (what Thompson and Zyontz call "conversion"). Overall, they find that of the 164,993 US authors who publish in genetic engineering, 1.81% ordered CRISPR tools in 2012-14, with an average success rate (subsequent CRISPR publication) of 11.30%. Interestingly, once they control for researcher quality, there is no location effect on experimenting with CRISPR—researchers in Cambridge and Berkeley were not more likely than similar researchers in other locations to order CRISPR tools. But location had a large effect on successful conversion into a publication: researchers were more successful with mammalian CRISPR use if they were located in Cambridge (where CRISPR was first successful with mammalian cells).

Zyontz's job talk paper, Running with (CRISPR) Scissors: Tool Adoption and Team Assembly, only has the abstract currently available online, though she quickly replied to my email asking about a draft. She digs deeper into these barriers to CRISPR adoption by quantifying the role of "external tool specialists" who aid in adopting and applying the technology. She takes advantage of natural differences in the difficulty of using CRISPR in the different areas. Here's how she summarized her results in an email:

In tool adoption cases, like CRISPR, where complementary know-how is needed, external tool specialists can provide that know-how across applications. External tool specialists are scientists that know CRISPR, but not necessarily the application area. But when such tool specialists are scarce and there is a rush to adopt the tool, teams have a choice of how to use external specialists. Either external specialists join teams that go after the easiest applications to get the tool to more areas faster (or just to publish more papers in general) or they join teams that go after the most complex problems where their human capital is more necessary. I find that external tool specialists contribute more to early adopter teams that provide innovations in difficult application areas, and not the low hanging fruit. In the easier applications, teams in the application area are more inclined to learn how to use CRISPR themselves for new innovations. Interestingly, this effect does not diminish right away. External tool specialists are still used for subsequent innovations in more difficult applications.

Legal scholars have discussed both barriers to accessing physical research tools and the importance of human capital in facilitating tacit knowledge transfer, but as with many issues of innovation law, there has been far too little evidence to inform these discussions. It is thus exciting to see this detailed exploration of knowledge diffusion in a particular technological field.